The present invention relates to crystalline epirubicin hydrochloride and to a method for its production.
Epirubicin and its acid addition salts, such as epirubicin hydrochloride, are compounds from a group of anthracyclines, which have been used since the 1980s as cytostatics for treatment of various types of solid tumors. The structure of epirubicin hydrochloride can be represented by the following formula:

The use of epirubicin for treatment of tumors is the subject of U.S. Pat. No. 5,091,373, for example.
The production of epirubicin is described in U.S. Pat. Nos. 4,112,076 and 5,874,550, among others. For example, epirubicin and its acid addition salts can be synthesized chemically starting from daunorubicin. The production of epirubicin by the fermentation of microorganisms, however, is also possible and disclosed, for example, in European patent application Publication No. EP 1 990 405. Organic and inorganic contaminants typically accumulate during the production of epirubicin, and their proportion can be up to 25 weight percent of the produced product mixture. For this reason, purification of epirubicin or its corresponding acid addition salts after production is essential.
A suitable method for purifying epirubicin hydrochloride emerges from U.S. Pat. No. 4,861,870. Here, epirubicin hydrochloride is precipitated from an aqueous solution with the help of acetone and is obtained as an amorphous solid. With this method it is possible to obtain amorphous epirubicin hydrochloride in largely pure form.
In U.S. Pat. No. 7,485,707 and International patent application Publication No. WO 2010/039159 there are described certain crystalline forms of epirubicin hydrochloride, which are characterized by different x-ray diffraction patterns, that exhibit improved thermal stability compared with known modifications of epirubicin hydrochloride. These crystalline modifications should be able to be obtained by precipitating epirubicin hydrochloride from a solution or a gel by adding hydrophilic organic solvent. With the post-processing of the method described in these patent documents, however, it was determined that crystalline epirubicin hydrochloride cannot be obtained with the described x-ray diffraction patterns under the specified conditions.
Furthermore, the problem is known from the prior art that the production or crystallization of epirubicin hydrochloride leads to an undesired formation of dimers and decomposition products, such as doxorubicinone.
Therefore, there is also a need for a thermally stable modification of crystalline epirubicin hydrochloride and a simple and reliable method for producing such a thermally stable modification of crystalline epirubicin hydrochloride in high purity.